Correlation of Immunohistochemistry and Fluorescence in Situ Hybridization for HER-2 Assessment in Breast Cancer Patients: Single Centre Experience

BACKGROUND: Accurate assessment of HER-2 is imperative in selecting patients for targeted therapy. Most commonly used test methods for HER-2 are immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH). We evaluated the concordance between FISH and IHC for HER-2 in breast cancer samples using Food and Drug Administration approved tests.MATERIAL AND METHODS: Archived paraffin tissue blocks from 73 breast cancer patients were used. HER-2 immunostaining was performed using Ventana anti–HER-2 monoclonal antibody. The FISH assay was performed using PathVysion™ HER-2 DNA Probe Kit.RESULTS: Of the 73 cases 68.5% were IHC 0/1+, 15.07% were IHC 2+ and 16.44% were IHC 3+. Successful hybridisation was achieved in 72 cases. HER-2 FISH amplification was determined in 16.67% cases. Ten IHC 3+ and two IHC 2+ cases were FISH positive. Two of the IHC 3+ cases were FISH negative. Concordance rate was 100%, 18.18% and 83.33% for IHC 0/1+, 2+ and 3+ group, respectively. Total concordance was 84.72%, kappa 0.598 (p < 0.0001). The sensitivity of IHC in detecting IHC 2+ and IHC 3+ cases was 16.7% and 83.3%, and the specificity was 85% and 96.67%, respectively.CONCLUSION: The consistency between the methods was highest for IHC negative and lowest for IHC equivocal cases. The immunohistochemistry showed high sensitivity for IHC 2+/3+ cases and high specificity for IHC 3+ cases. Our results support the view that false-positive rather than false-negative IHC results are a problem with HER-2/IHC testing, and that IHC should be used as an initial screening test, but IHC 2+/ 3+ results should be confirmed by FISH.

Download Full-text

SP3, a reliable alternative to HercepTest in determining HER-2/neu status in breast cancer patients

Journal of Clinical Pathology ◽

10.1136/jclinpath-2012-201270 ◽

2013 ◽

Vol 66 (5) ◽

pp. 409-414 ◽

Cited By ~ 1

Author(s):

Timothy Michael D'Alfonso ◽

Yi-Fang Liu ◽

Zhengming Chen ◽

Ying-Bei Chen ◽

Ashley Cimino-Mathews ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Core Biopsy ◽

In Situ Hybridisation ◽

Excisional Biopsy ◽

Needle Core Biopsy ◽

Breast Cancer Patients ◽

Biopsy Specimens ◽

Her 2

Accurate assessment of HER-2/neu gene status in breast cancer patients has important prognostic and therapeutic implications. Overexpression/gene amplification of HER-2 is associated with a more aggressive clinical course and eligibility for targeted therapy with trastuzumab. A variety of immunohistochemical (IHC) antibodies and in situ hybridisation (ISH) methods have been employed to assess HER-2 status. SP3 is a rabbit monoclonal antibody that has been shown to have a high level of agreement with other anti-HER-2 antibodies and ISH methods. We assessed HER-2 status by SP3 and HercepTest IHC stains and by fluorescence in situ hybridisation (FISH) on invasive breast carcinomas from paired needle core biopsy and excisional biopsy specimens from 100 patients. We compared the two antibodies with respect to concordance rates with FISH, concordance rates between samples of the same tumour, and sensitivity and specificity using FISH as the reference test. Concordance between SP3 and FISH in needle core biopsy and excisional biopsy specimens was 96% (95% CI 91.9% to 99.7%) (κ=0.89 (95% CI 0.73 to 1.00)) and 97% (95% CI 90.3% to 99.3%) (κ=0.84 (95% CI 0.66 to 1.00)), respectively. Sensitivity and specificity of SP3 for detecting HER-2 overexpression/gene amplification were 78.3% and 100%, respectively, in needle core biopsy and excisional biopsy specimens. Concordance between SP3 results assessed on the needle core biopsy and excisional biopsy was 89% (95% CI 81.2% to 94.4%) (κ=0.62 (95% CI 0.42 to 0.82)). Concordance between SP3 and HercepTest antibodies, after excluding 2+ cases, was 97.6% (95% CI 94.0% to 99.3%) (κ=0.88 (95% CI 0.77 to 1.00)). SP3 is a reliable alternative to HercepTest in evaluating HER-2 status in breast cancer patients. Like other anti-HER-2 antibodies, SP3 may serve as a diagnostic tool in breast pathology and has potential utility as an IHC biomarker in non-mammary malignancies.

Download Full-text

Comparison of Immunohistochemical and Fluorescence In Situ Hybridization Assessment for HER-2/neu Status in Taiwanese Breast Cancer Patients

Taiwanese Journal of Obstetrics and Gynecology ◽

10.1016/s1028-4559(07)60008-4 ◽

2007 ◽

Vol 46 (2) ◽

pp. 146-151 ◽

Cited By ~ 12

Author(s):

Shou-Jen Kuo ◽

Boris Bao-Tyan Wang ◽

Cheng-Shyong Chang ◽

Tze-Ho Chen ◽

Kun-Tu Yeh ◽

...

Keyword(s):

Breast Cancer ◽

In Situ Hybridization ◽

Fluorescence In Situ Hybridization ◽

Cancer Patients ◽

Breast Cancer Patients ◽

Her 2

Download Full-text

Chromogenic In Situ Hybridisation Test for Breast Cancer Patients with Equivocal IHC Results - a Study from Iran

Asian Pacific Journal of Cancer Prevention ◽

10.7314/apjcp.2015.16.17.7695 ◽

2015 ◽

Vol 16 (17) ◽

pp. 7695-7700 ◽

Cited By ~ 2

Author(s):

Mitra Mehrazma ◽

Elham Kalantari ◽

Hamid Rezvani ◽

Babak Bahar ◽

Ali Basi ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

In Situ Hybridisation ◽

Breast Cancer Patients

Download Full-text

HER-2 gene amplification by chromogenic in situ hybridisation (CISH) compared with fluorescence in situ hybridisation (FISH) in breast cancer—A study of two hundred cases

The Breast ◽

10.1016/j.breast.2005.09.008 ◽

2006 ◽

Vol 15 (4) ◽

pp. 519-527 ◽

Cited By ~ 39

Author(s):

A. Sáez ◽

F.J. Andreu ◽

M.A. Seguí ◽

M.L. Baré ◽

S. Fernández ◽

...

Keyword(s):

Breast Cancer ◽

Gene Amplification ◽

In Situ Hybridisation ◽

Fluorescence In Situ Hybridisation ◽

Her 2

Download Full-text

The Human Epidermal Growth Factor Receptor 2 Screening Tests for Breast Cancer Suggested by the New Updated Recommendation of the American Society of Clinical Oncology/College of American Pathologists Will Involve a Rise of the In-Situ Hybridization Tests for the European Laboratories of Pathology

ISRN Oncology ◽

10.1155/2014/793695 ◽

2014 ◽

Vol 2014 ◽

pp. 1-6 ◽

Cited By ~ 4

Author(s):

Christian Garbar ◽

Aude-Marie Savoye ◽

Corinne Mascaux ◽

Eva Brabencova ◽

Hervé Curé

Keyword(s):

Breast Cancer ◽

In Situ Hybridisation ◽

False Negative ◽

Growth Factor Receptor ◽

Screening Tests ◽

Fluorescence In Situ Hybridisation ◽

Her2 Positive ◽

Epidermal Growth ◽

American Society

Aims. The differences between the 2007 and the 2013 ASCO/CAP HER2 guidelines have been compared. We also discussed the potential consequences in our pathological practice. Material and Methodology. 189 HER2 fluorescence in situ hybridisation (FISH) tests were performed from 1016 preliminary HER2 immunohistochemical tests (IHC). All cases were reviewed and reclassed following the 2007 and 2013 ASCO/CAP recommendations. Results. The 2013 version decreased false-negative IHC (3/118 versus 1/54, P=ns) and created more 2+ IHC (40/186 versus 89/186, P=0.001) or more 3+ IHC (9/186 versus 39/186, P=0.001). One false-positive IHC was described for the 2013 version (0/9 versus 1/39, P=ns). Equivocal FISH was reduced (8/186 versus 2/186, P=ns). An estimation based on our data for 1000 patients showed a rise of our FISH tests for the control of 2+ IHC (180 tests for the 2007 version versus 274 tests for the 2013 version or FISH work overflow is +52%) and for the control of 2+/3+ IHC (300 for the 2007 version versus 475 for the 2013 version or FISH work overflow is +58%). Conclusions. The new 2013 ASCO/CAP guidelines have detected more HER2 positive cases but have increased the number of FISH tests.

Download Full-text